Pathological Findings of IgG4-Related Lung Disease



IgG4-related disease (IgG4-RD) causes temporally and spatially diverse lesions in systemic organs, with respiratory organ involvement now known to include the bronchi, bronchioles, alveolar wall, pleura, pulmonary vessels, and mediastinal lymph nodes. The histopathological features of the lesion site are a marked lymphoplasmacytic infiltrate, diffusely distributed IgG4-positive plasma cells, and obliterative inflammation of arteries and/or veins. Some non-neoplastic lung diseases, whose cause was hitherto unknown, may be encompassed in this disease. Many such disorders must now be reconsidered in light of information emerging about IgG4-RD.


Anaplastic Lymphoma Kinase Interstitial Pneumonia Anaplastic Large Cell Lymphoma Inflammatory Myofibroblastic Tumor Nonspecific Interstitial Pneumonia 



The authors thank Dr. Joanne E. Yi, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA, and Dr. Yasumasa Monobe, Department of Pathology, Kawasaki Hospital, Okayama, Japan, for their kind contribution of some figures for this chapter.


  1. 1.
    Matsui S, Taki H, Shinoda K, et al. Respiratory involvement in IgG4-related Mikulicz’s disease. Mod Rheumatol. 2012;22:31–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Zen Y, Kitagawa S, Minato H, et al. IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung. Hum Pathol. 2005;36:710–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Matsubara O, Tanliu NS, Kenney RM, Mark EJ. Inflammatory pseudotumors of the lung – progression from organizing pneumonia to fibrous histiocytoma or to plasma-cell granuloma in 32 cases. Hum Pathol. 1988;19:807–14.PubMedCrossRefGoogle Scholar
  4. 4.
    Zen Y, Inoue D, Kitao A, et al. IgG4-related lung and pleural disease: a clinicopathologic study of 21 cases. Am J Surg Pathol. 2009;33:1886–93.PubMedCrossRefGoogle Scholar
  5. 5.
    Yamamoto H, Yasuo M, Ito M, et al. Clinical features of central airway involvement in autoimmune pancreatitis. Eur Resp J. 2011;38:1233–26.CrossRefGoogle Scholar
  6. 6.
    Nakasone E, Fujisawa T, Mato N, et al. A case of IgG4-related lung disease with multiple infiltrative shadows, mediastinal lymphadenopathy and left endobronchial tumor. Kikanshigaku. 2010;32:498–503.Google Scholar
  7. 7.
    Hirano K, Kawabe T, Komatsu Y, et al. High-rate pulmonary involvement in autoimmune pancreatitis. Intern Med J. 2006;36:58–61.PubMedCrossRefGoogle Scholar
  8. 8.
    Taniguchi T, Hamasaki A, Okamoto M. A case of suspected lymphocytic hypophysitis and organizing pneumonia during maintenance therapy for autoimmune pancreatitis associated with autoimmune thrombocytopenia. Endocr J. 2006;53:563–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Shrestha B, Sekiguchi H, Colby TV, et al. Distinctive pulmonary histopathology with increased IgG4-positive plasma cells in patients with autoimmune pancreatitis: report of 6 and 12 cases with similar histopathology. Am J Surg Pathol. 2009;33:1450–62.PubMedCrossRefGoogle Scholar
  10. 10.
    Yousem SA, Tazelaar HD, Manabe T, et al. Inflammatory myofibroblastic tumour. In: Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC, editors. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC; 2004. p. 105–6.Google Scholar
  11. 11.
    Coffin CM, Hornick JL, Fletcher CDM. Inflammatory myofibroblastic tumor- comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J Surg Pathol. 2007;31:509–20.PubMedCrossRefGoogle Scholar
  12. 12.
    Yamamoto H, Yamaguchi H, Aishima S, et al. Inflammatory myofibroblastic tumor versus IgG4-related sclerosing disease and inflammatory pseudotumor: a comparative clinicopathologic study. Am J Surg Pathol. 2009;33:1330–40.PubMedCrossRefGoogle Scholar
  13. 13.
    Deshpande V, Chicano S, Finkelberg D, et al. Autoimmune pancreatitis: a systemic immune complex mediated disease. Am J Surg Pathol. 2006;30:1537–45.PubMedCrossRefGoogle Scholar
  14. 14.
    Yamashita K, Haga H, Kobayashi Y, et al. Lung involvement in IgG4-related lymphoplasmacytic vasculitis and interstitial fibrosis. Am J Surg Pathol. 2008;32:1620–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Pittaluga S, Wilson WH, Jaffe ES. Lymphomatoid granulomatosis. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, editors. WHO classification of tumours of haematopoietic and lymphoid tissue. Lyon: International Agency for Research on Cancer; 2008. p. 247–9.Google Scholar
  16. 16.
    Yonemori Y, Fujii T, Notohara K, et al. IgG4-related sclerosing disease: pulmonary lesions. Byori to Rinsho. 2009;27:42–9.Google Scholar
  17. 17.
    Yousem SA, Hochholzer L. Pulmonary hyalinizing granuloma. Am J Clin Pathol. 1987;87:1–6.PubMedGoogle Scholar
  18. 18.
    Kuramochi H, Kawai T, Yakumaru K, et al. Multiple pulmonary hyalinizing granulomas associated with systemic idiopathic fibrosis. Acta Pathol Jpn. 1991;41:375–82.PubMedGoogle Scholar
  19. 19.
    Sato Y, Kojima M, Takata K, et al. Multicentric Castleman’s disease with abundant IgG4-positive cells: a clinical and pathological analysis of six cases. J Clin Pathol. 2010;63:1084–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Chang SY, Keogh K, Lewis JE, et al. Increased IgG4-positive plasma cells in granulomatosis with polyangiitis: a diagnostic pitfall of IgG4-related disease. Int J Rheumatol. 2012;2012:121702.PubMedGoogle Scholar
  21. 21.
    Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181–92.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Health Administration CenterUniversity of ToyamaToyama cityJapan
  2. 2.Department of Anatomic PathologyKurashiki Central HospitalKurashikiJapan
  3. 3.Department of Respiratory MedicineKanazawa University School of MedicineKanazawaJapan

Personalised recommendations